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Actuación de enfermería ante el síndrome de resección transuretral en una histeroscopia quirúrgica

La histeroscopia es un procedimiento con finalidad terapéutica y de diagnóstico, permitiendo una visión directa de la cavidad uterina. Es relativamente sencillo pero no exento de complicaciones. La solución más comúnmente utilizada para la distensión es glicina 1.5% debi-do a su baja viscosidad, bajo costo, transparencia y compatibilidad con electrocirugía. Una de las complicaciones más temidas durante la cirugía histeroscópica es hemodilución por absorción de medios de distensión. Presentamos el caso de una mujer de 64 años, con ab-sorción excesiva de glicina durante una histeroscopia. Destacamos la importancia de una vigilancia continua y una comunicación efectiva entre el equipo quirúrgico: ginecólogo, anestesiólogo y equipo de enfermería. Sin duda, esto nos permite identificar los factores de riesgo que pueden prevenir la absorción intraoperatoria de estos fluidos, así como establecer un diagnóstico temprano y aplicar un tratamiento oportuno y eficaz para minimizar complicaciones.

The association between thrombotic and inflammatory biomarkers and lower‐extremity peripheral artery disease


Lower‐extremity peripheral artery disease (LEAD) is associated with increased rates of mortality and morbidity. The aim of this study was to evaluate the associations among inflammatory and thrombotic markers and lower‐extremity peripheral disease. A total of 280 patients were enrolled in this study. Of these patients, 152 patients had LEAD on peripheral angiography that was performed because of suspected lower‐extremity peripheral disease based on history, physical examination, and non‐invasive tests. The control group consisted of 128 patients without LEAD on peripheral angiography. Patients with LEAD were classified according to trans‐atlantic inter‐society consensus (TASC) II classification. Subsequently, patients in TASC A to B were defined as having mild to moderate peripheral artery disease, and those in TASC C to D were defined as having advanced peripheral artery disease. Thrombotic and inflammatory markers, such as the neutrophil‐to‐lymphocyte ratio (NLR), the high‐sensitivity C (hs‐C) reactive protein level, the monocyte‐to‐high‐density lipoprotein‐cholesterol ratio, the fibrinogen to albumin ratio (FAR), and whole‐blood viscosity at high shear rate (HSR) and low shear rate (LSR), were evaluated in this population. The NLR, the monocyte‐to‐high‐density lipoprotein‐cholesterol ratio, the FAR, and whole‐blood viscosity, both at a LSR and a HSR, were significantly higher in patients with lower‐extremity peripheral disease compared with patients without lower‐extremity peripheral disease. We determined that lower‐extremity peripheral disease severity was correlated with the NLR, monocyte‐to‐high‐density lipoprotein‐cholesterol ratio, FAR, whole‐blood viscosity at LSR, and whole‐blood viscosity at HSR (r = 0.719, P = .004; r = 0.25, P = .008; r = 0.691, P = .002; r = 0.546, P  < .001; and r = 0.448, P = .001, respectively). However hs‐C reactive protein levels were similar between patients with or without LEAD (2.47 ± 1.32 1.61 ± 0.91 P = .685). In addition, there was no correlation between the severity of LEAD and hs‐C reactive levels. In this study, we determined that the levels of inflammatory and thrombotic biomarkers are elevated in peripheral artery disease, and these levels predict disease severity.

Rapid enzymatic burn debridement: A review of the paediatric clinical trial experience


NexoBrid (NXB) has been proven to be an effective selective enzymatic debridement agent in adults. This manuscript presents the combined clinical trial experience with NXB in children. Hundred and ten children aged 0.5 to 18 years suffering from deep thermal burns of up to 67% total body surface area were treated with NXB in three clinical trials. Seventy‐seven children were treated with NXB in a phase I/II study, where 92.7% of the areas treated achieved complete eschar removal within 0.9 days from admission. Thirty‐three children (17 NXB, 16 standard of care [SOC]) participated in a phase III randomized controlled trial. All wounds treated with NXB achieved complete eschar removal. Time to complete eschar removal (from informed consent) was 0.9 days for NXB vs 6.5 days for SOC (P < .001). The incidence of surgical excision was 7.9% for NXB vs 73.3% for SOC (P < .001). Seventeen of these children participated in a phase III‐b follow‐up study (9 NXB and 8 SOC). The average long‐term modified Vancouver Scar Scale scores were 3.4 for NXB‐treated wounds vs 4.4 for SOC‐treated wounds (NS). There were no significant treatment‐related adverse events. Additional studies are needed to strengthen these results.

The prevalence, characteristics, and related factors of pressure injury in medical staff wearing personal protective equipment against COVID‐19 in China: A multicentre cross‐sectional survey


Since December 2019, the medical staff fighting against COVID‐19 frequently reported the device‐related pressure injury (DRPI) caused by personal protective equipment (PPE). We conducted a cross‐sectional survey online to investigate the prevalence and characteristics of DRPI among medical staff. Univariate and multivariate logistic regression analyses were employed to explore the risk factors associated with DRPI. A total of 4308 participants were collected and 4306 participants were valid from 161 hospitals in China. The overall prevalence of DRPI caused by PPE among medical staff was 30.03% (95% CI 28.69%‐31.41%). The prevalence of male was more than that of female (42.25%, 95% CI 37.99‐46.51% vs 26.36%, 95% CI 26.93‐29.80%, P  < .001).The categories were mainly stages 1 and 2, and the common anatomical locations were nose bridge, cheeks, ears, and forehead. Logistic regression analysis revealed that the risk factors were sweating (OR = 43.99, 95% CI 34.46‐56.17), male (OR = 1.50, 95% CI 1.12‐1.99), level 3 PPE (OR = 1.44, 95% CI 1.14‐1.83), and longer wearing time (OR = 1.28, 95% CI 0.97‐1.68). The prevalence of DRPI was high among medical staff wearing PPE against COVID‐19, and the risk factors were sweating, male, wearing level 3 PPE, and longer wearing time. Comprehensive preventive interventions should be taken.

Life expectancy and survival analysis of patients with diabetes compared to the non diabetic population in Bulgaria

by Konstantin Tachkov, Konstantin Mitov, Yordanka Koleva, Zornitsa Mitkova, Maria Kamusheva, Maria Dimitrova, Valentina Petkova, Alexandra Savova, Miglena Doneva, Dimitar Tcarukciev, Vasil Valov, Galia Angelova, Manoela Manova, Guenka Petrova


To evaluate the expected life expectancy in patients with diabetes in Bulgaria and to compare it to the expected life expectancy of the non-diabetic population in the country.


It is a retrospective observational population study on individuals diagnosed with diabetes, compared to the non-diabetic population in Bulgaria for the period 2012–2015. Data from the national diabetes register and national statistical institute were used to construct life-tables with probability of survival with t-test and Chi Square test. Confounder analysis was done by age, sex, and type of diabetes. All-cause mortality and deaths in diabetic patients were analyzed. Kaplan-Meier survival curves were constructed for each age group and a log-rank analysis was conducted.


Average life expectancy in the non-diabetic population, patients with Type 1 DM and with Type 2 DM is 74.8; 70.96 and 75.19 years, respectively. For 2012–2015 the mortality in the non-diabetic population remained constant and lower (average—1.48%) compared to type-1 DM (5.25%) and Type-2 (4.27%). Relative risk of death in diabetics was higher overall (12%), after the age of 70 before which the relative risk was higher for the non-diabetic population. This was observed as a trend in all analyzed years.


Patients with type 2 DM have a longer life-expectancy than patients with type-1 DM and overall Diabetics life expectancy equals that of the non-diabetic population, which could suggest improved disease control and its associated complications in Bulgaria. Male diabetics show slightly longer life expectancy than their counterparts in the non-diabetic population, by a marginal gain of 0.6 years for the entire observed period. Life expectancy in diabetic women increased by 1.3 years, which was not observed in the non-diabetic population. Prevalence of diabetes was higher for women. Improved diabetes control may explain this gain in life; however other studies are needed to confirm this.

The 2015-2016 El Niño increased infection parameters of copepods on Eastern Tropical Pacific dolphinfish populations

by Ana María Santana-Piñeros, Yanis Cruz-Quintana, Ana Luisa May-Tec, Geormery Mera-Loor, María Leopoldina Aguirre-Macedo, Eduardo Suárez-Morales, David González-Solís

The oceanographic conditions of the Pacific Ocean are largely modified by El Niño (EN), affecting several ecological processes. Parasites and other marine organisms respond to environmental variation, but the influence of the EN cycle on the seasonal variation of parasitic copepods has not been yet evaluated. We analysed the relation between infection parameters (prevalence and mean intensity) of the widespread parasitic copepods Caligus bonito and Charopinopsis quaternia in the dolphinfish Coryphaena hippurus and oceanography during the strong 2015–16 EN. Fish were collected from capture fisheries on the Ecuadorian coast (Tropical Eastern Pacific) over a 2-year period. Variations of sea surface temperature (SST), salinity, chlorophyll a (Chl-a), Oceanic Niño Index (ONI), total host length (TL) and monthly infection parameters of both copepod species were analysed using time series and cross-correlations. We used the generalised additive models for determine the relationship between environmental variables and infection parameters. The total body length of the ovigerous females and the length of the eggs of C. bonito were measured in both periods. Infection parameters of both C. bonito and Ch. quaternia showed seasonal and annual patterns associated with the variation of environmental variables examined (SST, salinity, Chl-a and ONI 1+2). Infection parameters of both copepod species were significantly correlated with ONI 1+2, SST, TL and Chl-a throughout the GAMLSS model, and the explained deviance contribution ranged from 16%-36%. Our results suggest than an anomaly higher than +0.5°C triggers a risen in infection parameters of both parasitic copepods. This risen could be related to increases in egg length, female numbers and the total length of the ovigerous females in EN period. This study provides the first evidence showing that tropical parasitic copepods are sensitive to the influence of EN event, especially from SST variations. The observed behaviour of parasitic copepods likely affects the host populations and structure of the marine ecosystem at different scales.

Oral administration with a traditional fermented multi-fruit beverage modulates non-specific and antigen-specific immune responses in BALB/c mice

by Jamie Bernadette A. Sy, Tsui-Chun Hsu, Aniket Limaye, Je-Ruei Liu

Fruits have been widely considered as the default “health foods” because they contain numerous vitamins and minerals needed to sustain human health. Fermentation strategies have been utilized to enhance the nutritive and flavor features of healthy and readily consumable fruit products while extending their shelf lives. A traditional fermented multi-fruit beverage was made from five fruits including kiwi, guava, papaya, pineapple, and grape fermented by Saccharomyces cerevisiae along with lactic acid bacteria and acetic acid bacteria. The immunomodulatory properties of the fermented multi-fruit beverage, in vivo nonspecific and ovalbumin (OVA)-specific immune response experiments using female BALB/c mice were performed. Administration of the fermented multi-fruit beverage reduced the calorie intake, thus resulting in a less weight gain in mice compared to the water (placebo)-fed mice. In the nonspecific immune study model, the fermented multi-fruit beverage enhanced phagocytosis and T cell proliferation but did not affect B cell proliferation and immunoglobulin G (IgG) production. Analysis of cytokine secretion profile also revealed that the fermented multi-fruit beverage enhanced proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and T helper (Th)1-related cytokine interferon (IFN)-γ production, thus creating an immunostimulatory effect. Nonetheless, in the specific immune study model, the results showed that the fermented multi-fruit beverage decreased the production of proinflammatory cytokines IL-6 and TNF-α production in OVA-immunized mice. Moreover, it also caused a decrease in the production of anti-OVA IgG1, which was accompanied by a decrease in Th2-related cytokines IL-4 and IL-5 production and an increase in Th1-related cytokine IFN-γ production, indicating that it may have the potential to shift the immune system from the allergen‐specific Th2 responses toward Th1-type responses. The results indicate that fermented multi-fruit beverage has the potential to modulate immune responses both in a nonspecific and specific manners.

Virulence factors and antibiograms of <i>Escherichia coli</i> isolated from diarrheic calves of Egyptian cattle and water buffaloes

by Nader M. Sobhy, Sarah G. A. Yousef, Hamada A. Aboubakr, Muhammad Nisar, Kakambi V. Nagaraja, Sunil K. Mor, Robert J. Valeris-Chacin, Sagar M. Goyal

Diarrhea caused by Escherichia coli in calves is an important problem in terms of survivability, productivity and treatment costs. In this study, 88 of 150 diarrheic animals tested positive for E. coli. Of these, 54 samples had mixed infection with other bacterial and/or parasitic agents. There are several diarrheagenic E. coli pathotypes including enteropathogenic E. coli (EPEC), Shiga-toxin producing E. coli (STEC), enterotoxigenic E. coli (ETEC) and necrotoxigenic E. coli (NTEC). Molecular detection of virulence factors Stx2, Cdt3, Eae, CNF2, F5, Hly, Stx1, and ST revealed their presence at 39.7, 27.2, 19.3, 15.9, 13.6, 9.0, 3.4, and 3.4 percent, respectively. As many as 13.6% of the isolates lacked virulence genes and none of the isolate had LT or CNF1 toxin gene. The odds of isolating ETEC from male calves was 3.6 times (95% CI: 1.1, 12.4; P value = 0.042) that of female calves, whereas the odds of isolating NTEC from male calves was 72.9% lower (95% CI: 91.3% lower, 15.7% lower; P value = 0.024) than that in females. The odds of isolating STEC in winter was 3.3 times (95% CI: 1.1, 10.3; P value = 0.037) that of spring. Antibiograms showed 48 (54.5%) of the isolates to be multi-drug resistant. The percent resistance to tetracycline, streptomycin, ampicillin, and trimethoprim-sulfamethoxazole was 79.5, 67.0, 54.5, and 43.0, respectively. Ceftazidime (14.8%), amoxicillin-clavulanic acid (13.6%) and aztreonam (11.3%) showed the lowest resistance, and none of the isolates was resistant to imipenem. The results of this study can help improve our understanding of the epidemiological aspects of E. coli infection and to devise strategies for protection against it. The prevalence of E. coli pathotypes can help potential buyers of calves to avoid infected premises. The antibiograms in this study emphasizes the risks associated with the random use of antibiotics.

Application of co-culture technology of epithelial type cells and mesenchymal type cells using nanopatterned structures

by Taek-Hee Jung, Eun-Bin Chung, Hyung Woo Kim, Seong Woo Choi, Soon-Jung Park, Anthony Safaa Mukhtar, Hyung-Min Chung, Eunmi Kim, Kang Moo Huh, Dong Sung Kim, Sun-Woong Kang, Sung-Hwan Moon

Various nanopatterning techniques have been developed to improve cell proliferation and differentiation efficiency. As we previously reported, nanopillars and pores are able to sustain human pluripotent stem cells and differentiate pancreatic cells. From this, the nanoscale patterns would be effective environment for the co-culturing of epithelial and mesenchymal cell types. Interestingly, the nanopatterning selectively reduced the proliferative rate of mesenchymal cells while increasing the expression of adhesion protein in epithelial type cells. Additionally, co-cultured cells on the nanopatterning were not negatively affected in terms of cell function metabolic ability or cell survival. This is in contrast to conventional co-culturing methods such as ultraviolet or chemical treatments. The nanopatterning appears to be an effective environment for mesenchymal co-cultures with typically low proliferative rates cells such as astrocytes, neurons, melanocytes, and fibroblasts without using potentially damaging treatments.

Association between attending exercise-based cardiac rehabilitation and cardiovascular risk factors at one-year post myocardial infarction

by Ingela Sjölin, Maria Bäck, Lennart Nilsson, Alexandru Schiopu, Margret Leosdottir


Randomized trials confirm the benefits of exercise-based cardiac rehabilitation on cardiovascular risk factors. Whether exercise-based cardiac rehabilitation provides the same favourable effects in real-life cardiac rehabilitation settings, in the modern era of myocardial infarction treatment, is less well known. We examined the association between attending exercise-based cardiac rehabilitation and improvements in cardiovascular risk factors at one-year post myocardial infarction in patients included in the Swedish heart disease registry, SWEDEHEART.


In this retrospective registry-based cohort study, we included 19 136 patients post myocardial infarction (75% men, 62.8±8.7 years) who were registered in SWEDEHEART between 2011 and 2013. The association between attending exercise-based cardiac rehabilitation (43% participation rate) and changes in cardiovascular risk profile between baseline and one-year follow-up was assessed using multivariable regression analysis adjusting for age, comorbidities and medication.


Attenders more often reported to have stopped smoking (men 64% vs 50%; women 64% vs 53%, p Conclusions

In an unselected registry cohort of patients post myocardial infarction, compared to non-attenders those attending exercise-based cardiac rehabilitation achieved significantly larger improvements in cardiovascular risk factors at one-year after the acute event.

Effect of experimental, morphological and mechanical factors on the murine spinal cord subjected to transverse contusion: A finite element study

by Marion Fournely, Yvan Petit, Eric Wagnac, Morgane Evin, Pierre-Jean Arnoux

Finite element models combined with animal experimental models of spinal cord injury provides the opportunity for investigating the effects of the injury mechanism on the neural tissue deformation and the resulting tissue damage. Thus, we developed a finite element model of the mouse cervical spinal cord in order to investigate the effect of morphological, experimental and mechanical factors on the spinal cord mechanical behavior subjected to transverse contusion. The overall mechanical behavior of the model was validated with experimental data of unilateral cervical contusion in mice. The effects of the spinal cord material properties, diameter and curvature, and of the impactor position and inclination on the strain distribution were investigated in 8 spinal cord anatomical regions of interest for 98 configurations of the model. Pareto analysis revealed that the material properties had a significant effect (p

Effect of minimally invasive autopsy and ethnic background on acceptance of clinical postmortem investigation in adults

by I. M. Wagensveld, A. C. Weustink, J. A. Kors, B. M. Blokker, M. G. M. Hunink, J. W. Oosterhuis


Autopsy rates worldwide have dropped significantly over the last five decades. Imaging based autopsies are increasingly used as alternatives to conventional autopsy (CA). The aim of this study was to investigate the effect of the introduction of minimally invasive autopsy, consisting of CT, MRI and tissue biopsies on the overall autopsy rate (of CA and minimally invasive autopsy) and the autopsy rate among different ethnicities.


We performed a prospective single center before-after study. The intervention was the introduction of minimally invasive autopsy as an alternative to CA. Minimally invasive autopsy consisted of MRI, CT, and CT-guided tissue biopsies. Autopsy rates over time and the effect of introducing minimally invasive autopsy were analyzed with a linear regression model. We performed a subgroup analysis comparing the autopsy rates of two groups: a group of western-European ethnicity versus a group of other ethnicities.


Autopsy rates declined from 14.0% in 2010 to 8.3% in 2019. The linear regression model showed a significant effect of both time and availability of minimally invasive autopsy on the overall autopsy rate. The predicted autopsy rate in the model started at 15.1% in 2010 and dropped approximately 0.1% per month (β = -0.001, p Conclusions

The introduction of the minimally invasive autopsy had a small, but significant effect on the overall autopsy rate. Furthermore, the minimally invasive autopsy appears to be more acceptable than CA among people with an ethnicity other than western-European.

30-year trends in major cardiovascular risk factors in the Czech population, Czech MONICA and Czech post-MONICA, 1985 – 2016/17

by Renata Cífková, Jan Bruthans, Peter Wohlfahrt, Alena Krajčoviechová, Pavel Šulc, Marie Jozífová, Lenka Eremiášová, Jan Pudil, Aleš Linhart, Jiří Widimský Jr, Jan Filipovský, Otto Mayer Jr, Zdenka Škodová, Rudolf Poledne, Petr Stávek, Věra Lánská


Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy.


There were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25–64 years).


Over the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p p p Conclusions

The significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic.

Confocal Raman microscopy to identify bacteria in oral subgingival biofilm models

by Lukas Simon Kriem, Kevin Wright, Renzo Alberto Ccahuana-Vasquez, Steffen Rupp

The study of oral disease progression, in relation to the accumulation of subgingival biofilm in gingivitis and periodontitis is limited, due to either the ability to monitor plaque in vitro. When compared, optical spectroscopic techniques offer advantages over traditional destructive or biofilm staining approaches, making it a suitable alternative for the analysis and continued development of three-dimensional structures. In this work, we have developed a confocal Raman spectroscopy analysis approach towards in vitro subgingival plaque models. The main objective of this study was to develop a method for differentiating multiple oral subgingival bacterial species in planktonic and biofilm conditions, using confocal Raman microscopy. Five common subgingival bacteria (Fusobacterium nucleatum, Streptococcus mutans, Veillonella dispar, Actinomyces naeslundii and Prevotella nigrescens) were used and differentiated using a 2-way orthogonal Partial Least Square with Discriminant Analysis (O2PLS-DA) for the collected spectral data. In addition to planktonic growth, mono-species biofilms cultured using the ‘Zürich Model’ were also analyzed. The developed method was successfully used to predict planktonic and mono-species biofilm species in a cross validation setup. The results show differences in the presence and absence of chemical bands within the Raman spectra. The O2PLS-DA model was able to successfully predict 100% of all tested planktonic samples and 90% of all mono-species biofilm samples. Using this approach we have shown that Confocal Raman microscopy can analyse and predict the identity of planktonic and mono-species biofilm species, thus enabling its potential as a technique to map oral multi-species biofilm models.

Cost‐effectiveness of multi‐layered silicone foam dressings for prevention of sacral and heel pressure ulcers in high‐risk intensive care unit patients: An economic analysis of a randomised controlled trial


Pressure ulcer incidence is high in intensive care units. This causes a serious financial burden to healthcare systems. We evaluated the cost‐effectiveness of multi‐layered silicone foam dressings for prevention of sacral and heel pressure ulcers in addition to standard prevention in high‐risk intensive care units patients. A randomised controlled trial to assess the efficacy of multi‐layered silicone foam dressings to prevent the development of pressure ulcers on heels and sacrum among 422 intensive care unit patients was conducted. Direct costs for preventive dressings in the intervention group and costs for treatment of incident pressure ulcers in both groups were measured using a bottom‐up approach. A cost‐effectiveness analysis by calculating the incremental cost‐effectiveness ratio using different assumptions was performed. Additional dressing and labour costs of €150.81 (€116.45 heels; €34.36 sacrum) per patient occurred in the intervention group. Treatment costs were €569.49 in the control group and €134.88 in the intervention group. The incremental cost‐effectiveness ratio was €1945.30 per PU avoided (€8144.72 on heels; €701.54 sacrum) in the intervention group. We conclude that application of preventive dressings is cost‐effective for the sacral area, but only marginal on heels for critically ill patients.

Can a teacher-led mindfulness intervention for new school entrants improve child outcomes? Protocol for a school cluster randomised controlled trial

Por: Quach · J. L. · Deery · B. · Kern · M. · Clinton · J. · Gold · L. · Orsini · F. · Sciberras · E.

The first years of school are critical in establishing a foundation for positive long-term academic, social and well-being outcomes. Mindfulness-based interventions may help students transition well into school, but few robust studies have been conducted in this age group. We aim to determine whether compared with controls, children who receive a mindfulness intervention within the first years of primary school have better: (1) immediate attention/short-term memory at 18 months post-randomisation (primary outcome); (2) inhibition, working memory and cognitive flexibility at 18 months post-randomisation; (3) socio-emotional well-being, emotion-regulation and mental health-related behaviours at 6 and 18 months post-randomisation; (4) sustained changes in teacher practice and classroom interactions at 18 months post-randomisation. Furthermore, we aim to determine whether the implementation predicts the efficacy of the intervention, and the cost effectiveness relative to outcomes.

Methods and analysis

This cluster randomised controlled trial will be conducted in 22 primary schools in disadvantaged areas of Melbourne, Australia. 826 students in the first year of primary school will be recruited to detect between groups differences of Cohen’s d=0.25 at the 18-month follow-up. Parent, teacher and child-assessment measures of child attention, emotion-regulation, executive functioning, socio-emotional well-being, mental health-related behaviour and learning, parent mental well-being, teacher well-being will be collected 6 and 18 months post-randomisation. Implementation factors will be measured throughout the study. Intention-to-treat analyses, accounting for clustering within schools and classes, will adopt a two-level random effects linear regression model to examine outcomes for the intervention versus control students. Unadjusted and analyses adjusted for baseline scores, baseline age, gender and family socioeconomic status will be conducted.

Ethics and dissemination

Ethics approval has been received by the Human Research Ethics Committee at the University of Melbourne. Findings will be reported in peer-review publications, national and international conference presentations and research snapshots directly provided to participating schools and families.

Pre-Results Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12619000326190).

Validation of a simplified score for predicting latent rheumatic heart disease progression using a prospective cohort of Brazilian schoolchildren

Por: Bechtlufft · B. M. · Nascimento · B. R. · Sable · C. · Fraga · C. L. · Barbosa · M. M. · Reis · S. D. · Diamantino · A. C. · Meira · Z. M. A. · Castilho · S. R. T. · Arantes · N. F. · Oliveira · K. K. · Silva · J. L. P. · Rezende · B. D. F. · Costa · W. A. A. · Mata · M. D. · Pereira

Echocardiographic (echo) screening is an important tool to estimate rheumatic heart disease (RHD) prevalence, but the natural history of screen-detected RHD remains unclear. The PROVAR+ (Programa de RastreamentO da VAlvopatia Reumática) study, which uses non-experts, telemedicine and portable echo, pioneered RHD screening in Brazil. We aimed to assess the mid-term evolution of Brazilian schoolchildren (5–18 years) with echocardiography-detected subclinical RHD and to assess the performance of a simplified score consisting of five components of the World Heart Federation criteria, as a predictor of unfavourable echo outcomes.


Public schools of underserved areas and private schools in Minas Gerais, southeast Brazil.


A total of 197 patients (170 borderline and 27 definite RHD) with follow-up of 29±9 months were included. Median age was 14 (12–16) years, and 130 (66%) were woman. Only four patients in the definite group were regularly receiving penicillin.

Primary and secondary outcome measures

Unfavourable outcome was based on the 2-year follow-up echo, defined as worsening diagnostic category, remaining with mild definite RHD or development/worsening of valve regurgitation/stenosis.


Among patients with borderline RHD, 29 (17.1%) progressed to definite, 49 (28.8%) remained stable, 86 (50.6%) regressed to normal and 6 (3.5%) were reclassified as other heart diseases. Among those with definite RHD, 13 (48.1%) remained in the category, while 5 (18.5%) regressed to borderline, 5 (18.5%) regressed to normal and 4 (14.8%) were reclassified as other heart diseases. The simplified echo score was a significant predictor of RHD unfavourable outcome (HR 1.197, 95% CI 1.098 to 1.305, p


The simple risk score provided an accurate prediction of RHD status at 2-year follow-up, showing a good performance in Brazilian schoolchildren, with a potential value for risk stratification and monitoring of echocardiography-detected RHD.

Biomarkers of exposure and early effect in three contaminated sites of southern Italy: protocols for etiological epidemiological studies

Por: Gorini · F. · Bustaffa · E. · Bolignano · D. · Cori · L. · Faita · F. · Gastaldelli · A. · Interdonato · M. · Minichilli · F. · Quattrone · G. · Squadrito · F. · Tripepi · G. · Vassalle · C. · Bianchi · F.

Environmental pollution has been progressively becoming one of the main risk factors to human diseases. In particular, populations living in high-contaminated sites are particularly exposed to environmental toxicants, with consequent increased risks to human health. In Italy, there are currently ongoing three epidemiological etiological studies aimed at evaluating the association between exposure to inorganic and organic chemicals and presence of biological markers of early effects in population living in three National Priority Contaminated Sites (NPCSs). Specifically, the correlations concern preclinical indicators of liver disease in Priolo NPCS, thyroid diseases in Milazzo-Valle del Mela NPCS and cardiovascular risk and kidney damage in Crotone NPCS.

Methods and analysis

Overall, approximately 1300 subjects of both sexes will be enrolled in the three NPCSs according to specific inclusion criteria. For each subject, serum and urine specimens are collected, on which the determination of biological markers of exposure and early effects for the selected outcomes are performed. Individual information on environmental and occupational exposure, medical history, diet and life habits is obtained through questionnaires provided by web platform. In Milazzo-Valle del Mela and Crotone NPCSs, not invasive instrumental and imaging examinations are performed in order to evaluate further risk factors of thyroid carcinoma and cardiovascular disease, respectively.

Ethics and dissemination

The protocol studies have been approved by the Ethics Committees responsible for the three involved NPCSs: the Ethics Committee ‘Catania 2’ for the NPCS of Priolo (21 July 2017, n. 500/2017/CECT2), the Ethics Committee of the University Hospitals of Messina for the NPCS of Milazzo-Valle del Mela (19 February 2018, n.2/2018); the Ethics Committee of the Region of Calabria for the NPCS of Crotone (20 July 2017, n. 174). Results will be disseminated among policy-makers, citizens, stakeholders and scientific community through the organisation of conferences and events, and the publication on international peer/reviewed journals.

Lung cancer survival and mortality in Taiwan following the initial launch of targeted therapies: an interrupted time series study

Por: Hsu · J. C. · Wei · C.-F. · Yang · S.-C. · Lin · P.-C. · Lee · Y.-C. · Lu · C. Y.

Two oral targeted therapies, gefitinib and erlotinib, were first approved and then launched into the market for treatment of late-stage non-small cell lung cancer (NSCLC) in Taiwan in 2003 and 2006, respectively. The aim of this study were to determine the trends in lung cancer burden and examine changes in lung cancer-related survival rates and mortality following the launch of these new drugs.


Yearly lung cancer-related data (1994–2013), including incidence, number of newly diagnosed patients, survival rate and mortality, were retrieved from the Taiwan Cancer Registry Database.

Design and outcome measures

Using a time series design with autoregressive integrated moving average model, we investigated and projected trends in the incidence and early diagnosis of lung cancer in Taiwan. We also estimated the changes in survival rates and mortality following the launch of targeted therapies using interrupted time series and segmented regression models.


The age-standardised incidence of lung cancer increased from 22.53 per 100 000 people in 1994 to 34.09 in 2013, and it was projected to reach 38.98 by 2020. The rate of early-stage NSCLC at diagnosis increased from 12.63% in 2004 to 23.99% in 2013, and it was projected to reach 32.95% by 2020. The 2-year lung cancer survival increased by 19.81% (95% CI 14.90% to 24.71%) 3 years following the launch of gefitinib. Lung cancer mortality declined by 5.97% (95% CI –8.20% to –3.73%) 3 years following the launch of gefitinib.


Lung cancer survival rate increased and mortality decreased significantly following the launch of gefitinib and erlotinib in Taiwan.